Spermatogonial stem cells (SSCs) maintain spermatogenesis in the postnatal testis. These adult tissue stem cells may provide a cell-based therapy for treating infertility that sometimes results from chemotherapy or radiation treatments (e.g., for cancer or prior to bone marrow transplantation). Theoretically, SSCs can be isolated and cryopreserved prior to the toxic therapy and then reintroduced into the testes of the patient upon completion of treatment and/or cure. Thus, through autologous transplantation of SSCs, it may be possible for male survivors to recover natural fertility and father their own genetic children. The proof-in-principle for this approach is already established mice, rats and goats. In addition, we recently developed a nonhuman primate model with long-term infertility secondary to high dose chemotherapy that will allow us to transfer these ideas to a species with greater relevance to human physiology. Spermatogenesis is a highly conserved process in mammals, so it is tempting to speculate that techniques to isolate, cryopreserve and transplant SSCs can eventually be translated to humans. However, this needs to be confirmed experimentally. Three specific aims are designed to examine, in human tissues, some of the critical feasibility and safety issues associated with SSC transplantation. PUBLIC HEALTH RELEVANCE: Chemotherapy and radiation treatments for cancer can cause permanent infertility. Spermatogonial stem cell (SSC) transplantation is an experimental procedure that may offer fertile hope to cancer survivors. Critical feasibility and safety issues must be addressed before this new fertility preserving technology can be translated to the clinic. This application will provide initial insights about stem cell activity in normal human testis tissues and optimize techniques for human SSC isolation, enrichment and cryopreservation.